Pulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades,... Show morePulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades, diagnosing PE is still a difficult process due to the non-specific symptoms, which can frequently overlap with symptoms of other cardiopulmonary diseases. Currently recommended diagnostic strategies for suspected acute PE consist of standardized assessment of the clinical pre-test probability (CPTP) using validated clinical decision rules (CDRs) and D-dimer testing. PE is considered safely ruled out in patients with a non-high CPTP and a normal D-dimer test. Imaging tests as computed tomography pulmonary angiography (CTPA) are required in the case of a high CPTP and/or abnormal D-dimer test to confirm the diagnosis. The first part of this thesis describes the challenges of diagnosing PE in general and in specific clinically relevant patient subgroups. Moreover, this part evaluates the diagnostic performance of non-invasive diagnostic strategies for suspected PE in specific relevant patient subgroups. The second part of this thesis focuses on venous thrombotic complications in hospitalized patients with COVID-19. Show less
Boeijen, J.A.; Pol, A.C. van de; Uum, R.T. van; Smit, K.; Ahmad, A.; Rijswijk, E. van; ... ; Zwart, D.L.M. 2023
ObjectiveDuring the COVID-19 pandemic new collaborative-care initiatives were developed for treating and monitoring COVID-19 patients with oxygen at home. Aim was to provide a structured overview... Show moreObjectiveDuring the COVID-19 pandemic new collaborative-care initiatives were developed for treating and monitoring COVID-19 patients with oxygen at home. Aim was to provide a structured overview focused on differences and similarities of initiatives of acute home-based management in the Netherlands.MethodsInitiatives were eligible for evaluation if (i) COVID-19 patients received oxygen treatment at home; (ii) patients received structured remote monitoring; (iii) it was not an ‘early hospital discharge’ program; (iv) at least one patient was included. Protocols were screened, and additional information was obtained from involved physicians. Design choices were categorised into: eligible patient group, organization medical care, remote monitoring, nursing care, and devices used.ResultsNine initiatives were screened for eligibility; five were included. Three initiatives included low-risk patients and two were designed specifically for frail patients. Emergency department (ED) visit for an initial diagnostic work-up and evaluation was mandatory in three initiatives before starting home management. Medical responsibility was either assigned to the general practitioner or hospital specialist, most often pulmonologist or internist. Pulse-oximetry was used in all initiatives, with additional monitoring of heart rate and respiratory rate in three initiatives. Remote monitoring staff’s qualification and authority varied, and organization and logistics were covered by persons with various backgrounds. All initiatives offered remote monitoring via an application, two also offered a paper diary option.ConclusionsWe observed differences in the organization of interprofessional collaboration for acute home management of hypoxemic COVID-19 patients. All initiatives used pulse-oximetry and an app for remote monitoring. Our overview may be of help to healthcare providers and organizations to set up and implement similar acute home management initiatives for critical episodes of COVID-19 (or other acute disorders) that would otherwise require hospital care. Show less
By examining the iconised photographs of the COVID-19 pandemic, published under the heading of The Great Empty by the New York Times in March 2020, this article explores the aesthetic operations... Show more By examining the iconised photographs of the COVID-19 pandemic, published under the heading of The Great Empty by the New York Times in March 2020, this article explores the aesthetic operations and ethical implications of representing anxiety through photographing desolate landscapes. To do so, it situates these images within the genre of late photography, also known as aftermath photography, to discuss how emptiness can function as a surrogate for anxiety. First, by foregrounding the unique temporality of the landscape genre in photography, it examines the aesthetic dimension of seeing deserted places in photographs. By shifting its focus from the image to its caption, it then discusses how the caption of such photographs can interpolate an ethical dimension onto them. Finally, by drawing on Giorgio Agamben’s philosophy of “gesture,” the article puts forward that the combination of aestheticized photographs with ethicised captions in The Great Empty expresses anxiety as a mode of gesturality: a sui generis communicational mode that simultaneously galvanizes and paralyzes the viewer. Show less
Bazdar, S.; Berg, S. van den; Rutjes, N.W.; Bloemsma, L.D.; Downward, G.S.; Weger, L.A. de; ... ; Kapitein, B. 2023
BackgroundThe incidence of severe asthma exacerbations (SAE) requiring a pediatric intensive care unit (PICU) admission during the coronavirus disease 2019 (COVID-19) pandemic (and its association... Show moreBackgroundThe incidence of severe asthma exacerbations (SAE) requiring a pediatric intensive care unit (PICU) admission during the coronavirus disease 2019 (COVID-19) pandemic (and its association with public restrictions) is largely unknown. We examined the trend of SAE requiring PICU admission before, during, and after COVID-19 restrictions in Amsterdam, the Netherlands, and its relationship with features such as environmental triggers and changes in COVID-19 restriction measures.MethodsIn this single-center, retrospective cohort study, all PICU admissions of children aged >= 2 years for severe asthma at the Amsterdam UMC between 2018 and 2022 were included. The concentrations of ambient fine particulate matter (PM2.5) and pollen were obtained from official monitoring stations.ResultsBetween January 2018 and December 2022, 228 children were admitted to the PICU of the Amsterdam UMC for SAE. While we observed a decrease in admissions during periods of more stringent restriction, there was an increase in the PICU admission rate for SAE in some periods following the lifting of restrictions. In particular, following the COVID-19 restrictions in 2021, we observed a peak incidence of admissions from August to November, which was higher than any other peak during the indicated years. No association with air pollution or pollen was observed.ConclusionWe hypothesize that an increase in clinically diagnosed viral infections after lockdown periods was the reason for the altered incidence of SAE at the PICU in late 2021, rather than air pollution and pollen concentrations. Show less
In dit onderzoek hebben we de rol van thromboinflammatie onderzocht in verschillende hoog-risico populaties, zoals mensen met type 2 diabetes mellitus (T2DM) en patiënten met ernstige COVID-19, als... Show moreIn dit onderzoek hebben we de rol van thromboinflammatie onderzocht in verschillende hoog-risico populaties, zoals mensen met type 2 diabetes mellitus (T2DM) en patiënten met ernstige COVID-19, als ook naar verhoogd risico bij vrouwen in de Nederlandse samenleving. Thromboinflammatie is de verbinding tussen de gelijktijdige activatie van de stollingsroute en immuunrespons welke een belangrijke trigger vormt voor bloedvat schade, prominent in microvasculaire gezondheid. Als eerste laten we zien dat er genderspecifieke associaties zijn tussen het activatie potentieel van de stollingsroute en microvasculaire gezondheid met betrekking tot eventueel ontwikkelen van hartfalen. Het mechanisme van T2DM progressie varieert bij verschillende etniciteiten en we hebben aangetoond dat veranderingen in cholesterol functie (HDL) en lipiden profiel in het bloed een van de onderliggende mechanismen kunnen zijn die leiden tot versnelde ziekte progressie bij Zuid-Aziaten van Nederlandse afkomst met T2DM in vergelijk met Nederlandse blanke Europeanen met T2DM. Met nieuwe geavanceerde technieken vonden we ook dat bij patiënten met ernstige COVID-19 factoren in het bloed aanwezig zijn die schade aan de kleine bloedvaten en verhoogde stollingsactiviteit teweegbrengen. Ook bij deze patiënten zagen we dat veranderingen in HDL compositie een belangrijke rol in de ernst van de ziekte speelt. Samen geven de resultaten het belang aan van thromboinflammatie in verhoogd-risico populaties in versneld ontwikkelen van hartfalen, T2DM en COVID-19. Het onderzoek laat de noodzaak zien van vroege detectie in het proces, waarbij vroegtijdige interventies kunnen lijden tot preventie of het beter managen van het thromboinflammatoire ziekteproces.*************************************************************************In this study, we investigated the role of thromboinflammation in various high-risk populations, including individuals with type 2 diabetes mellitus (T2DM) and patients with severe COVID-19, as well as the increased risk in women in Dutch society. Thromboinflammation refers to the simultaneous activation of the clotting pathway and immune response, which is a significant trigger for vascular damage, particularly in microvascular health.Firstly, we demonstrated sex-specific associations between coagulation parameters and microvascular health. The mechanism of T2DM progression varies among different ethnicities, and we found that changes in cholesterol function (HDL) and lipid profiles in the blood could be underlying mechanisms leading to accelerated disease progression in South Asians of Dutch descent with T2DM compared to Dutch white Caucasian with T2DM.Using advanced techniques, we also identified factors in the blood of patients with severe COVID-19 that contribute to small blood vessel damage and increased clotting activity. We observed that changes in HDL composition played an important role in the severity of the disease in these patients.Overall, our results highlight the importance of thromboinflammation in high-risk populations in the accelerated development of heart failure, T2DM, and COVID-19. The research emphasizes the need for early detection in the process, where timely interventions can lead to prevention or better management of the thromboinflammatory disease process. Show less
ObjectivesDelirium is a serious condition, which poses treatment challenges during hospitalisation for COVID-19. Improvements in testing, vaccination and treatment might have changed patient... Show moreObjectivesDelirium is a serious condition, which poses treatment challenges during hospitalisation for COVID-19. Improvements in testing, vaccination and treatment might have changed patient characteristics and outcomes through the pandemic. We evaluated whether the prevalence and risk factors for delirium, and the association of delirium with in-hospital mortality changed through the pandemic.MethodsThis study was part of the COVID-OLD study in 19 Dutch hospitals including patients ≥70 years in the first (spring 2020), second (autumn 2020) and third wave (autumn 2021). Multivariable logistic regression models were used to study risk factors for delirium, and in-hospital mortality. Differences in effect sizes between waves were studied by including interaction terms between wave and risk factor in logistic regression models.Results1540, 884 and 370 patients were included in the first, second and third wave, respectively. Prevalence of delirium in the third wave (12.7%) was significantly lower compared to the first (22.5%) and second wave (23.5%). In multivariable-adjusted analyses, pre-existing memory problems was a consistent risk factor for delirium across waves. Previous delirium was a risk factor for delirium in the first wave (OR 4.02), but not in the second (OR 1.61) and third wave (OR 2.59, p-value interaction-term 0.028). In multivariable-adjusted analyses, delirium was not associated with in-hospital mortality in all waves.ConclusionDelirium prevalence declined in the third wave, which might be the result of vaccination and improved treatment strategies. Risk factors for delirium remained consistent across waves, although some attenuation was seen in the second wave. Show less
Aims The COVID-19 pandemic impacted diabetes care by reducing diabetes outpatient visits and diabetes-related screening due to allocation of healthcare resources. Yet the impact of COVID-19 on... Show moreAims The COVID-19 pandemic impacted diabetes care by reducing diabetes outpatient visits and diabetes-related screening due to allocation of healthcare resources. Yet the impact of COVID-19 on diabetes outpatients has not been extensively evaluated. This study aimed to assess the effect of the COVID-19 pandemic on diagnostics and intermediate outcomes of outpatient diabetes care pre- and during COVID.Methods This observational cohort study included 8,442 diabetes patients in the Dutch Pediatric and Adult Registry of Diabetes (DPARD) visiting diabetes outpatient clinics in 2019 and 2021. A mixed-effects regression analysis was used to examine differences in target achievement of HbA1c, BMI, blood pressure, LDL-cholesterol, eGFR, and the difference in mean HbA1c between 2019 and 2020 among n = 1,426 outpatients who visited in both years. Analyses were adjusted for age, sex, and BMI.Results A 22.7% (21.6-23.8%, p < 0.001) decline in outpatient volume was observed during the pandemic (2020). BMI, lipid spectrum, kidney function, and HbA1c were assessed less frequently in 2020 than in 2019. In 2020, compared to 2019, the median HbA1c level increased by 2.2% (1.0 mmol/mol, p = 0.035) and the percentages of patients with known HbA1C meeting targets below 10, 8, 7% (86, 64, and 53 mmol/mol) decreased by 0.5%, 1.7% and 1.4%, respectively. Target blood pressure <= 130/80 mmHg was achieved more often in 2020 (15.0% versus 18.3%, p = 0.018), while HbA1c <= 86 mmol/mol was achieved less (89.3% versus 87.1%, p = 0.001), among diabetes outpatients seen in both 2019 and 2020. In patients visiting both years, HbA1c was 2.3% (1.9 mmol/l, 95% CI 1.2-2.5, p < 0.001) lower during the pandemic than in the prepandemic (2019).Conclusions The COVID pandemic was associated with a marked reduction in patient volume in diabetes outpatient care among five hospitals. Among patients who received outpatient care both before and during the pandemic period, HbA1c control and blood pressure control enhanced during the pandemic. Re-evaluation of current diabetes outpatient care organization is warranted to ensure optimal diabetes care in future times. Show less
Leegwater, E.; Dol, L.; Benard, M.R.; Roelofsen, E.E.; Delfos, N.M.; Feltz, M. van der; ... ; Nieuwkoop, C. van 2023
IntroductionRemdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients’ respiratory insufficiency seemed to... Show moreIntroductionRemdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients’ respiratory insufficiency seemed to recover particularly rapidly after initiation of remdesivir. In this study, we investigated if this rapid improvement was caused by remdesivir, and which patient characteristics might predict a rapid clinical improvement in response to remdesivir.MethodsThis was a multicentre observational cohort study of hospitalised patients with COVID-19 who required supplemental oxygen and were treated with dexamethasone. Rapid clinical improvement in response to treatment was defined by a reduction of at least 1 L of supplemental oxygen per minute or discharge from the hospital within 72 h after admission. Inverse probability of treatment-weighted logistic regression modelling was used to assess the association between remdesivir and rapid clinical improvement. Secondary endpoints included in-hospital mortality, ICU admission rate and hospitalisation duration.ResultsOf 871 patients included, 445 were treated with remdesivir. There was no influence of remdesivir on the occurrence of rapid clinical improvement (62% vs 61% OR 1.05, 95% CI 0.79–1.40; p = 0.76). The in-hospital mortality was lower (14.7% vs 19.8% OR 0.70, 95% CI 0.48–1.02; p = 0.06) for the remdesivir-treated patients. Rapid clinical improvement occurred more often in patients with low C-reactive protein (≤ 75 mg/L) and short duration of symptoms prior to hospitalisation (< 7 days) (OR 2.84, 95% CI 1.07–7.56).ConclusionRemdesivir generally does not increase the incidence of rapid clinical improvement in hospitalised patients with COVID-19, but it might have an effect in patients with short duration of symptoms and limited signs of systemic inflammation. Show less
The treatment of community-acquired pneumonia (CAP) is based on early diagnosis and swift initiation of appropriate antibiotic treatment. Despite effective treatment, CAP is still one of the... Show moreThe treatment of community-acquired pneumonia (CAP) is based on early diagnosis and swift initiation of appropriate antibiotic treatment. Despite effective treatment, CAP is still one of the leading causes of morbidity and mortality due to infectious diseases worldwide. This thesis aimed to identify strategies to optimise the treatment of hospitalised CAP patients outside an intensive care unit (ICU) setting with a focus on corticosteroid treatment. First, this thesis focused on the question whether oral adjunctive corticosteroid treatment improves outcomes in hospitalised CAP patients and tries to identify a subgroup of CAP patients, based on inflammatory status at admission, in whom the beneficial effects of adjunctive corticosteroid treatment outweigh the disadvantages associated with corticosteroid use. Next, this thesis investigated whether obesity and overweight are associated with worse clinical outcomes in a population of hospitalised COVID-19 patients who were all treated with the recommended 6 mg dexamethasone dose. Last, this thesis focused on optimising antibiotic treatment by exploring whether extensive microbiological testing facilitates early antibiotic alterations in CAP patients. Show less
Introduction: Nanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher... Show moreIntroduction: Nanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher vaccine acceptance, which is important for future mass vaccination campaigns to control outbreaks, such as COVID-19, and for public vaccination in general. In this study we investigated the safety and immunogenicity of needle-free intradermal delivery of a fractional third or fourth dose of mRNA-1273 vaccine by npMNA.Methods: This study was an open-label, randomised-controlled, proof-of-concept study. Healthy adults were eligible if they had received a primary immunisation series against SARS-CoV-2 with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) mRNA vaccine. A history of a COVID-19 infection or booster vaccination with mRNA-1273 or BNT162b2 was allowed if it occurred at least three months before inclusion. Participants were randomised in a 1:1 ratio to receive 20 & mu;g mRNA-1273 vaccine, either through npMNA patch applied on the skin (ID-patch group), or through intramuscular (IM) injection (IM-control group). Primary outcomes were reactogenicity up to two weeks after vaccination, and fold-increase of SARS-CoV-2 spike S1specific IgG antibodies 14 days post-vaccination.Results: In April 2022, 20 participants were enroled. The geometric mean concentration (GMC) did not increase in the ID-patch group after vaccination, in contrast to the IM-control group (GMC was 1,006 BAU/mL (95% CI 599-1,689), 3,855 (2,800-5,306), and 3,513 (2,554-4,833) at day 1, 15 and 29, respectively). In addition, SARSCoV-2-specific T cell responses were lower after ID vaccination through npMNA.Conclusion: Needle-free delivery of 20 & mu;g mRNA-1273 vaccine by npMNA failed to induce antibody and T cell responses. As this is a potentially very useful vaccination method, it is important to determine which adjustments are needed to make this npMNA successful. Clinical trial registry (on ClinicalTrial.gov): NCT05315362. Show less
Arend, B.W.H. van der; Bloemhof, M.M.; Schoor, A.G. van der; Zwet, E.W. van; Terwindt, G.M. 2023
BackgroundThis longitudinal cohort study aimed to investigate changes in migraine-related outcomes following COVID-19 infection and vaccination.MethodsWe identified 547 clinically diagnosed... Show moreBackgroundThis longitudinal cohort study aimed to investigate changes in migraine-related outcomes following COVID-19 infection and vaccination.MethodsWe identified 547 clinically diagnosed migraine patients from the Leiden Headache Center who kept a headache E-diary during the COVID-19 pandemic (February 2020 to August 2022). We sent a questionnaire to register their COVID-19 infection and/or vaccination dates. After applying inclusion criteria, n = 59 participants could be included in the infection analysis and n = 147 could be included in the vaccination analysis. Primary outcome was the change in monthly migraine days (MMD) between 1 month prior and 1 month post COVID-19 infection or vaccination. Secondary outcome variables were change in monthly headache days (MHD) and monthly acute medication days (MAMD).ResultsVaccination against COVID-19 was associated with an increase in MMD (1.06; 95% confidence interval [CI] = 0.57–1.55; p < 0.001), MHD (1.52; 95% CI = 0.91–2.14; p < 0.001) and MAMD (0.72; 95% CI = 0.33–1.12; p < 0.001) in the first month post-vaccination. COVID-19 infection solely increased the number of MAMD (1.11; 95% CI = 0.10–1.62; p < 0.027), but no statistically significant differences in MMD or MHD were observed.ConclusionsOur findings imply that vaccination against COVID-19 is associated with an increase in migraine, indicating a possible role of inflammatory mediators in migraine pathophysiology. Show less
Hoogervorst, L.A.; Stijnen, P.; Albini, M.; Janda, N.; Stewardson, A.J.; Patel, K.; ... ; Marang-van de Mheen, P. 2023
Objectives To assess across seven hospitals from six different countries the extent to which the COVID-19 pandemic affected the volumes of orthopaedic hospital admissions and patient outcomes for... Show moreObjectives To assess across seven hospitals from six different countries the extent to which the COVID-19 pandemic affected the volumes of orthopaedic hospital admissions and patient outcomes for non-COVID-19 patients admitted for orthopaedic care.Design A multi-centre interrupted time series (ITS) analysis.Setting Seven hospitals from six countries who collaborated within the Global Health Data@Work collaborative.Participants Non-COVID-19 patients admitted for orthopaedic care during the pre-pandemic (January/2018-February/2020) and COVID-19 pandemic (March/2020-June/2021) period. Admissions were categorised as: (1) acute admissions (lower limb fractures/neck of femur fractures/pathological fractures/joint dislocations/upper limb fractures); (2) subacute admissions (bone cancer); (3) elective admissions (osteoarthritis).Outcome measures Monthly observed versus expected ratios (O/E) were calculated for in-hospital mortality, long (upper-decile) length-of-stay and hospital readmissions, with expected rates calculated based on case-mix. An ITS design was used to estimate the change in level and/or trend of the monthly O/E ratio by comparing the COVID-19 pandemic with the pre-pandemic period.Results 69221 (pre-pandemic) and 22940 (COVID-19 pandemic) non-COVID-19 orthopaedic patient admissions were included. Admission volumes were reduced during the COVID-19 pandemic for all admission categories (range: 33%-45%), with more complex patients treated as shown by higher percentages of patients admitted with >= 1 comorbidity (53.8% versus 49.8%, p<0.001). The COVID-19 pandemic was not associated with significant changes in patient outcomes for most diagnostic groups. Only for patients diagnosed with pathological fractures (pre-pandemic n=1671and pandemic n=749), the COVID-19 pandemic was significantly associated with an immediate mortality reduction (level change of -77.7%, 95%CI -127.9% to -25.7%) and for lower limb fracture patients (pre-pandemic n=9898and pandemic n=3307) with a significantly reduced trend in readmissions (trend change of -6.3% per month, 95%CI -11.0% to -1.6%).Conclusions Acute, subacute, as well as elective orthopaedic hospital admissions volumes were reduced in all global participating hospitals during the COVID-19 pandemic, while overall patient outcomes for most admitted non-COVID-19 patients remained the same despite the strain caused by the surge of COVID-19 patients. Show less
Background: Videos have been an important medium for providing health and risk communication to the public during the COVID-19 pandemic. Public health officials, health care professionals, and... Show moreBackground: Videos have been an important medium for providing health and risk communication to the public during the COVID-19 pandemic. Public health officials, health care professionals, and policy makers have used videos to communicate pandemic-related content to large parts of the population. Evidence regarding the outcomes of such communication, along with their determinants, is however limited.Objective: The aim of this study was to test the impact of nonvisual information factors of video communication on 4 outcomes: trust, comprehension, intentions, and behavior.Methods: Twelve short health communication videos related to pandemics were produced and shown to a large sample of participants, applying a randomized controlled between-subjects design. Three factors were included in the creation of the videos: the topic (exponential growth, handwashing, and burden of pandemics on the health care system), the source (expert and nonexpert), and a call to action (present or absent). Participants were randomly assigned to 1 video intervention, and 1194 valid replies were collected. The data were analyzed using factorial ANOVA.Results: The 3 pandemic-related topics did not affect trust, comprehension, intentions, or behavior. Trust was positively influenced by an expert source (2.5%), whereas a nonexpert source instead had a positive effect on the proxy for behavior (5.7%) compared with the expert source. The inclusion of a call to action had a positive effect on both trust (4.1%) and comprehension (15%).Conclusions: Trust and comprehension in pandemic-related video communication can be enhanced by using expert sources and by including a call to action, irrespective of the topic being communicated. Intentions and behavior appear to be affected to a small extent by the 3 factors tested in this study. Show less
IntroductionNanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher... Show moreIntroductionNanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher vaccine acceptance, which is important for future mass vaccination campaigns to control outbreaks, such as COVID-19, and for public vaccination in general. In this study we investigated the safety and immunogenicity of needle-free intradermal delivery of a fractional third or fourth dose of mRNA-1273 vaccine by npMNA.MethodsThis study was an open-label, randomised-controlled, proof-of-concept study. Healthy adults were eligible if they had received a primary immunisation series against SARS-CoV-2 with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) mRNA vaccine. A history of a COVID-19 infection or booster vaccination with mRNA-1273 or BNT162b2 was allowed if it occurred at least three months before inclusion. Participants were randomised in a 1:1 ratio to receive 20 µg mRNA-1273 vaccine, either through npMNA patch applied on the skin (ID-patch group), or through intramuscular (IM) injection (IM-control group). Primary outcomes were reactogenicity up to two weeks after vaccination, and fold-increase of SARS-CoV-2 spike S1-specific IgG antibodies 14 days post-vaccination.ResultsIn April 2022, 20 participants were enroled. The geometric mean concentration (GMC) did not increase in the ID-patch group after vaccination, in contrast to the IM-control group (GMC was 1,006 BAU/mL (95% CI 599–1,689), 3,855 (2,800–5,306), and 3,513 (2,554–4,833) at day 1, 15 and 29, respectively). In addition, SARS-CoV-2-specific T cell responses were lower after ID vaccination through npMNA.ConclusionNeedle-free delivery of 20 µg mRNA-1273 vaccine by npMNA failed to induce antibody and T cell responses. As this is a potentially very useful vaccination method, it is important to determine which adjustments are needed to make this npMNA successful. Show less
Oymans, E.J.; Kroon, C.D. de; Bart, J.; Nijman, H.W.; Aa, M.A. van der 2023
Objective: To study the impact of the COVID-19 pandemic and consequent lockdown on the number of diagnoses of gynaecological malignancies in the Netherlands.Methods: We performed a retrospective... Show moreObjective: To study the impact of the COVID-19 pandemic and consequent lockdown on the number of diagnoses of gynaecological malignancies in the Netherlands.Methods: We performed a retrospective cohort study using data from the Netherlands Cancer Registry (NCR) on women of 18 years and older diagnosed with invasive endometrial, ovarian, cervical or vulvar cancer in the period 2017-2021. Analyses were stratified for age, socioeconomical status (SES) and region.Results: The incidence rate of gynaecological cancer was 67/100.000 (n = 4832) before (2017-2019) and 68/ 100.000 (n = 4833) during (2020) the COVID-19 pandemic. Comparing the number of diagnoses of the two periods for the four types of cancer separately showed no significant difference. During the first wave of COVID19 (March-June 2020), a clear decrease in number of gynaecological cancer diagnoses was visible (20-34 %). Subsequently, large increases in number of diagnoses were visible (11-29 %). No significant differences in incidence were found between different age groups, SES and regions. In 2021 an increase of 5.9 % in number of diagnoses was seen.Conclusion: In the Netherlands, a clear drop in number of diagnoses was visible for all four types of gynaecological cancers during the first wave, with a subsequent increase in number of diagnoses in the second part of 2020 and in 2021. No differences between SES groups were found. This illustrates good organisation of and access to health care in the Netherlands. Show less
This dissertation aimed to examine the ethnic socialization context in the upbringing of Chinese-Dutch children, specifically three social-contextual factors: parents, children’s books, and the... Show moreThis dissertation aimed to examine the ethnic socialization context in the upbringing of Chinese-Dutch children, specifically three social-contextual factors: parents, children’s books, and the COVID pandemic. Results reveal that Chinese-Dutch children evaluate their ingroup and the White outgroup most positively, followed by the Middle Eastern and North African (MENA) outgroup, and the Black outgroup least positively. Stronger maternal endorsement of multiculturalism is associated with lower child ethnic prejudice (in terms of less ingroup preference). In addition, results demonstrate maternal self-report ethnic-racial socialization strategies and the observed behaviors that reflect color-evasiveness and white normativity. Furthermore, results show an overrepresentation of White authors, illustrators, and characters, and a preference for light skin color in East Asian characters in illustrations in Chinese children’s books, suggesting a form of current postcolonial influences on Chinese children’s literature. Furthermore, results indicate ethnicity-related attitude differences among mothers participating after than before the COVID outbreak, with higher perceived discrimination and stronger ethnic identity. A lower ingroup rejection among Chinese-Dutch children was found in the post-COVID-outbreak group than in the pre-COVID-outbreak group. This dissertation can foster a better understanding of the interethnic relations in the underrepresented Chinese group and elucidate the ethnicity-related consequences of the pandemic in this group. Show less
Atmowihardjo, L.N.; Schippers, J.R.; Duijvelaar, E.; Bartelink, I.H.; Bet, P.M.; Swart, N.E.L.; ... ; Aman, J. 2023
Purpose A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed... Show morePurpose A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed pulmonary capillary leak in preclinical studies and improved clinical outcomes in hospitalized COVID-19 patients. We investigated the effect of intravenous (IV) imatinib on pulmonary edema in COVID-19 ARDS. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial. Invasively ventilated patients with moderate-to-severe COVID-19 ARDS were randomized to 200 mg IV imatinib or placebo twice daily for a maximum of seven days. The primary outcome was the change in extravascular lung water index (.EVLWi) between days 1 and 4. Secondary outcomes included safety, duration of invasive ventilation, ventilator-free days (VFD) and 28-day mortality. Posthoc analyses were performed in previously identified biological subphenotypes. Results 66 patients were randomized to imatinib (n = 33) or placebo (n = 33). There was no difference in.EVLWi between the groups (0.19 ml/kg, 95% CI - 3.16 to 2.77, p = 0.89). Imatinib treatment did not affect duration of invasive ventilation (p = 0.29), VFD (p = 0.29) or 28-day mortality (p = 0.79). IV imatinib was well-tolerated and appeared safe. In a subgroup of patients characterized by high IL-6, TNFR1 and SP-D levels (n = 20), imatinib significantly decreased EVLWi per treatment day (- 1.17 ml/kg, 95% CI - 1.87 to - 0.44). Conclusions IV imatinib did not reduce pulmonary edema or improve clinical outcomes in invasively ventilated COVID-19 patients. While this trial does not support the use of imatinib in the general COVID-19 ARDS population, imatinib reduced pulmonary edema in a subgroup of patients, underscoring the potential value of predictive enrichment in ARDS trials. Show less
Purpose:The aim of this study was to evaluate the cases of herpes simplex and zoster ophthalmicus after SARS-CoV-2 vaccination and assess the clinical presentations in patients.Methods:A... Show morePurpose:The aim of this study was to evaluate the cases of herpes simplex and zoster ophthalmicus after SARS-CoV-2 vaccination and assess the clinical presentations in patients.Methods:A retrospective analysis of cases reported to the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS) between December 11, 2020, and July 1, 2022. Patients diagnosed with herpes simplex ophthalmicus (HSO) and herpes zoster ophthalmicus (HZO) after vaccination with BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Janssen) were included in the study. We performed a descriptive analysis of patient demographics, history, and ophthalmic and systemic clinical presentations. The correlations between vaccine type and continuous variables were assessed by the one-way analysis of variance test. In addition, we used the Pearson chi(2) test to assess the association between 3 vaccines and categorical variables. A post hoc analysis was performed between HSO and HZO onset intervals after vaccination, dose, and vaccine type. The 30-day risk analysis was also performed for HSO and HZO onset postvaccination using the reverse Kaplan-Meier analysis.Results:A total of 1180 cases of HZO (983, 83.30%) and HSO (180, 15.25%) were reported. The mean age of patients with HZO and HSO was 59.02 +/- 19.05 and 52.68 +/- 17.83 years, respectively. Most of the cases of HZO (795, 80.87%) and HSO (131, 72.78%) were reported in patients who received BNT162b2. In the cohort, 63.28% and 65.56% diagnosed with HZO and HSO were women. About one third of HZO (36.52%) and HSO (35.56%) cases were reported after the first dose. More than half of the cases of HZO (61.34%) and HSO (64.45%) were reported within the first 2 weeks after vaccination. The estimated crude reporting rate (per million doses) in the United States was 0.25, 0.22, and 0.47 for BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively. The onset interval for HZO was significantly shorter in patients who received BNT162b2 (20.51 +/- 56.20 days, P = 0.030) compared with patients who received mRNA-1273 (36.56 +/- 108.67 days) and Ad26.COV2.S (39.66 +/- 60.15 days) vaccines. The 30-day risk analysis showed a significantly higher risk of HZO after BNT162b2 than the other 2 vaccines (P = 0.011).Conclusions:The low crude reporting rate suggests that HZO and HSO after SARS-CoV-2 vaccination occur rarely. This study provides insights into the possible temporal association between reported HSO and HZO after SARS-CoV-2 vaccines; however, further investigations are required to delineate the possible underlying immunological mechanisms. Show less
Koekenbier, E.L.; Fohse, K.; Maat, J.S. van de; Oosterheert, J.J.; Nieuwkoop, C. van; Hoogerwerf, J.J.; ... ; BCG-PRIME Study Grp 2023
ObjectivesTo test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more... Show moreObjectivesTo test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more comorbidities.MethodsCommunity-dwelling adults aged 60 years or older with one or more underlying comorbidities and no contraindications to BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for 6 months. The primary endpoint was a self-reported, test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTIs (i.e. RTIs including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine-Gray regression, accounting for competing events.ResultsA total of 6112 participants with a median age of 69 years (interquartile range, 65–74) and median of 2 (interquartile range, 1–3) comorbidities were randomized to BCG (n = 3058) or placebo (n = 3054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients [hazard ratio (HR), 1.12; 95% CI, 0.87–1.44]. COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR, 0.86; 95% CI, 0.46–1.61). During the study period, 13 BCG recipients died compared with 18 placebo recipients (HR, 0.71; 95% CI, 0.35–1.43), of which 11 deaths (35%) were COVID-19-related: six in the placebo group and five in the BCG group.Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR, 0.92; 95% CI, 0.66–1.28).DiscussionBCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization, or clinically relevant RTIs. Show less
